Although all FDA meetings play a critical role in any sponsor’s development strategy, when it comes to cell and gene therapies, the most valuable FDA interaction is arguably the very first: the INTERACT meeting. During the INTERACT meeting, sponsors can obtain initial, nonbinding advice from FDA regarding chemistry, manufacturing and controls (CMCs); pharmacology and toxicology; and the clinical aspects of their development program. This informal meeting should take place prior to any pivotal nonclinical studies, but after the sponsor has a good understanding of the manufacturing process. If managed wisely and well prepared for, the INTERACT meeting can prove invaluable in gaining early input from FDA regarding the evidence and detail needed to understand and evaluate the risk-benefit profile of your specific therapy. And that feedback is essential to de-risking and accelerating the development process.
Want to make the most of your INTERACT meeting? Consider these six tips:
1. Keep in mind that each cell and gene therapy is new to FDA reviewers. Precisely because the science behind these cutting-edge therapies is so new and evolving, the majority of these therapies have unknown or limited safety profiles, utilize complex manufacturing technologies, incorporate new devices and use cutting-edge testing methodologies. That means that FDA reviewers are facing a steep learning curve as they review novel cell and gene therapy applications. INTERACT meetings in large part acknowledge this reality, by providing sponsors with the opportunity to collaborate with and solicit feedback from FDA, early on in their development plans.
2. Commit to key manufacturing process and delivery device decisions prior to your INTERACT meeting. Some developers may be tempted to use their INTERACT meeting to present FDA with multiple manufacturing process or delivery device options – so they can leverage FDA feedback to help guide their selection process. This is a mistake. FDA reviewers expect developers to have already committed to manufacturing and delivery device decisions before the INTERACT meeting. Importantly, these selections may necessitate change or adjustment based on feedback from the FDA review team. The meeting is intended as an opportunity for developers to solicit FDA feedback to their development plans and decisions – not for the FDA to help sponsors choose from a range of potential options.
3. Be prepared to ask specific, targeted questions. Some of the most frequent mistakes developers make during their valuable INTERACT meeting are not asking specific-enough questions or not providing enough background information on their product and delivery device in the briefing packet to solicit adequate feedback from the agency. Also, in preparation of the meeting, the onus is on the sponsor to prioritize the specific topic areas and questions on which additional FDA feedback is needed. Generally speaking, the meeting discussion is limited to the initial questions submitted in the meeting package. The onus is also on the sponsor to ensure that the questions asked are specific and targeted; and that they’ve provided the agency with enough detail information and data to enable them to provide meaningful guidance.
4. Don’t avoid tough or potentially concerning issues. If there are specific issues or topics that you are concerned may slow down development, don’t rely on the FDA to flag those issues when they review your briefing packet and avoid developing that false sense of security stating “if FDA didn’t comment then it’s not a regulatory concern.” Instead, be sure to highlight and prioritize those concerns and request that the FDA review those priority issues. Also plan to request that FDA discuss those thorny issues at the beginning of the INTERACT meeting, so you have ample time to listen to their feedback. Do you need input regarding your plans to scale up your manufacturing processes to accommodate your first-in-human study? Guidance regarding whether the quality of your proposed raw materials will be appropriate in a GMP environment? Confirmation that your proposed drug delivery device is appropriate for your pre-clinical animal studies and will support use of the intended delivery device for your first-in-human study? It’s far more beneficial to get FDA feedback to these issues early on in your development process, versus in the final stages, when negative feedback could mean costly rework and delays. The bottom line: “show your hand – and put your cards on the table” and ask the tough, specific questions, early.
5. Ensure all key members of your development team are “on call” and available to quickly review FDA comments to your INTERACT meeting questions. Approximately 90 days in advance of your INTERACT meeting, you’ll provide the agency with an extensive briefing packet, outlining initial details about your product ranging from CMC controls to pharmacology and toxicology details, along with specific questions for FDA feedback. FDA will respond to those questions in writing in advance of the meeting, but typically only a day prior to your INTERACT meeting. It’s crucial that key members from your development team are prepared to thoroughly yet quickly review all of FDA’s written feedback before the INTERACT meeting takes place. This will enable your team, in turn, to prioritize topic areas for discussion and ensure every minute of the INTERACT meeting itself is spent soliciting additional FDA guidance relating to any written feedback with which you disagree or need more detail to understand.
6. Take thorough meeting minutes, so you can address all FDA feedback in your next submission. INTERACT meetings are nonbinding, and FDA attendees will not generate meeting minutes – but be sure to task someone on your team, in advance, with taking thorough minutes during the meeting. You’ll want to incorporate all meeting feedback into your development plan and Pre-IND meeting packet, documenting how you’ve addressed each FDA concern. This can be facilitated with a simple chart that tracks each FDA recommendation, how the recommendation was addressed, and where in the packet FDA reviewers can quickly find documentation that their feedback was addressed.
Cell and gene therapy development programs are highly complex — and managing them effectively requires well-planned interactions with the FDA through all stages of development – starting with the INTERACT meeting. FDA reviewers are committed to helping you and your product move forward. These six considerations can help you start your relationship with the FDA on the right foot, by leveraging your INTERACT meeting as an opportunity to gain the invaluable insight you need to accelerate the development of your therapy.
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